The long-term goal of this project is the establishment of conditions and procedures for bringing about the transfer of genetic material from one type of mammalian cell to another, and for its establishment in the recipient cell with the production of a stable transformed clone. In the shorter term, we hope to perfect methods for the preparation and enrichment of specific genetic material, and to characterize the cellular processes involved in its penetration, replication, expression and establishment in recipient cells. As donor genetic material we will use DNA, chromatin, chromosome fragments, and whole chromosomes. The DNA will be either free, packaged in membrane vesicles, or packaged as pseudovirions. The recipient cells will be derived from mutant mouse and human lines that are HGPRT minus (hypoxanthine-guanine phosphoribosyl transferase). The donors will be HGPRT plus revertant types with distinctive HGPRT proteins. The donor genetic material will be treated to enrich it for the proportion of HGPRT genes. Various conditions, including the stage in the division cycle of synchronized recipient cells, will be investigated for their effects on penetration, replication, expression and integration of donor genetic material.